• beta cells
• dopaminergic neurons
• neurotoxins
• dopaminergic drugs
• pesticides.

The main aim of my thesis is to investigate the role of the dopaminergic system in pancreatic β- cells’ physiology and to underline similarities between dopaminergic neurons and β-cells concerning the sensibility to toxins and pharmacological agents capable to protect both cell types. My dissertation is divided into five themed chapters: the role of the dopaminergic system in β-cells; the pharmacology of dopaminergic drugs affecting β-cells function and viability; to study the correlation between Parkinson and diabetes in terms of epidemiology; to analyse the effect of parkinsonian neurotoxins on β-cells survival; to analyse protective factors for the toxicity induced by neurotoxins.
More specifically, data from several studies suggest that neurotoxins like 1-methyl-4- phenylpyridinium (MPP+), 6-hydroxydopamine (6-OHDA) and rotenone are extremely toxic to dopaminergic neurons. Furthermore, epidemiological studies have highlighted how parkinsonian patients are more likely to develop type 2 diabetes and vice versa. Another characteristic that have in common dopaminergic neurons and β-cells is the expression of dopamine receptors (D1–D5), dopamine transporter and enzymes for dopamine production (tyrosine hydroxylase and aromatic amino-acid decarboxylase) and degradation (MAO-A and B). With these premises, we investigated if there are similarities between β-cells and dopaminergic neurons in terms of vulnerability to different toxins.
The cell lines analyzed are rat insulinoma cell line (INS-1 832/13) and mouse insulinoma cell line (MIN6). We showed that rotenone is the most potent for reducing β-cells viability and altering mitochondrial structure and bioenergetics in the low nanomolar range, similar to that found in dopaminergic cell lines. MPP+ and 6-OHDA show comparative impacts yet at higher concentration. Rotenone-induced toxicity was counteracted by α-tocopherol and partially by metformin, which are endowed with strong antioxidative and cytoprotective properties.
The methodological procedure taken in this study is a mixed approach based on the evaluation of toxicity on different cell lines, the analysis of cell morphology after exposure to toxic substances, the analysis of mitochondrial functionality and verification of the protection induced by some compounds like dopamine agonists, metformin and α-tocopherol. Regarding mitochondrial functionality, I have deepened the generation of ROS and associated signalling.
These experiments have allowed us to understand the relevance of some dopaminergic elements present in β-cells, at a physiological, pharmacological level and with regard to cellular vulnerability to environmental toxins, thus offering new potential therapeutic targets for both the treatment of diabetes and Parkinson's.